1. Field of the Invention
This invention relates to novel sulfates of monoalkyl esters of glutathione (.gamma.-L-glutamyl-L-cysteinylglycine) at the glycine carboxylic acid (hereinafter abbreviated as "glutathione monoester sulfates"), and to a process for producing the same.
2. Description of the Prior Art
An animal test showed that glutathione monoesters, unlike glutathione itself, are able to transfer into many types of cells at high concentrations and undergo hydrolysis in the cells to return back to glutathione [Proc. Natl. Acad. Sci. U.S.A., Vol.80, 5258 (1983)]. Hence glutathione monoesters are useful as easy-to-absorb, active derivatives of glutathione which effectively exhibit in living bodies glutathione's pharmacological activities, such as detoxication and radioprotective effects.
There is no literature discussing acid addition salts of glutathione monoesters (formed by esterification of glutathione by common methods), except the above-mentioned report in which description is made only of hydrochlorides of glutathione monoesters. That report, however, presents no detailed description on how the hydrochlorides had been prepared, but states that these salts were synthesized according to the method shown in Bergmann M. and Zervas L.; Z. Physiol. Chem., Vol.221, 51-54 (1933). Method of Bergmann, et al. is concerned with the synthesis of .gamma.-ethyl ester of glutamic acid by reaction of the acid with ethanol in the presence of hydrochloric acid. Therefore it may be deduced that the authors of the above-mentioned paper [Proc. Natl. Acad. Sci. U.S.A., Vol.80, 5258 (1983)] prepared the hydrochlorides of glutathione monoesters by direct esterification of glutathione with ethanol (or methanol) in the presence of hydrochloric acid.
Hydrochlorides of glutathione monoesters, however, cannot be isolated as crystals and hence tend to contain diesters as impurity. Diesters of glutathione, unlike monoesters, are toxic compounds and must be completely removed. Sulfates of glutathione monoesters of this invention are novel compounds which are highly crystallizable and hence can be purified very easily. Thus the process of this invention is capable of easily affording pure glutathione monoesters free from such toxic diesters.